The long term goal of this research project is to increase our understanding of the wound healing process. Over the next four years, our studies will focus on wound contraction using in vitro collagen matrix contraction models. Specific aims are as follows: (l) Analysis of the mechanoregulated mechanism of platelet derived growth factor (PDGF) receptor modulation: Studies will be carried out to determine if modulation of PDGF receptors depends on decreased receptor kinase activity or on increased protein tyrosine phosphatase activity. (2) Analysis of the contraction regulated cyclic AMP signaling pathway: Studies will be carried out to determine the roles of Ca2+, PKC, and cytoplasmic phospholipase A2 in adenylyl cyclase activation following stress relaxation. (3) Analysis of keloid fibroblasts using the collagen matrix contraction model: Studies will be carried out to compare keloid cell growth and extracellular matrix synthesis in mechanically stressed vs. relaxed collagen matrices. (4) Analysis of regulatory mechanisms for fibroblast contractility. Regulation of fibroblast contractility by protein kinases will be studied and compared under different mechanical conditions. (5) Analysis of the role of ectocytotic vesicles in extracellular matrix remodeling. Matrix vesicles released by fibroblasts during stress relaxation will be analyzed to learn if they bind or activate metalloproteinases involved in matrix remodeling.